The objectives of this proposal are to: (a) delineate the barriers to the passage of macromolecules during ultrafiltration in the normal glomerulus; and (b) determine the mechanisms responsible for disturbances of glomerural barrier function in proteinuric states. An important aspect of our approach is the ultrastructural identification of endogenous protein distribution (using peroxidase- labeled Fab fragments of antibodies against rat albumin or IgG) under physiological hemodynamic flow conditions (using Munich-Wistar rats with superficial glomeruli, on or close to the renal surface, and accessible to rapid fixation in situ). By a correlation of the morphologic findings with parallel functional data for normal and nephrotic glomeruli, the proposed studies aim to clarify the dynamics of normal and abnormal glomerular permeability.